褪黑素通过HIF-1α/VEGF信号通路减轻急性肾损伤的研究  

Study on melatonin alleviated acute kidney injury through the HIF-1α/VEGF pathway

作　　者：冯杰[1] 佟小雅 俞佳丽[3] 潘祉谕 查艳[2] 

机构地区：[1]贵州省人民医院儿科,贵州贵阳550002 [2]贵州省人民医院肾内科,贵州贵阳550002 [3]贵州医科大学免疫教研室,贵州贵阳550004

出　　处：《中国当代医药》2016年第29期12-15,共4页China Modern Medicine

基　　金：贵州省科学技术基金项目(黔科合J字[2012]2230号)

摘　　要：目的 探讨脂多糖（LPS）诱导的急性肾损伤中低氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的表达及褪黑素（Mel）对其表达的影响。方法 选取3~5周龄的30只Sprague-Dawley（SD）大鼠作为研究对象,随机分为对照组（n=10）、LPS组（n=10,静脉注射500μg/kg LPS）、Mel＋LPS组（n=10,注射LPS之前15 min给予Mel）。48 h后采用TBA法检测肾组织的丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性,分别用RT-q PCR和免疫组化检测HIF-1α、VEGF m RNA和蛋白表达水平。结果 LPS组肾小管上皮细胞肿胀、肾间质水肿,有炎细胞浸润;Mel＋LPS组的上述表现明显减轻。LPS组血清BUN和Scr含量[（35.56±1.83）mmol/L和（46.23±2.87）μmol/L]显著高于对照组[（12.69±0.97）mmol/L和（16.73±1.26）μmol/L]以及Mel＋LPS组[（23.17±1.33）mmol/L和（35.67±2.25）μmol/L]（P〈0.05）。LPS组小鼠肾组织的MDA水平[（697.45±43.13）nmol/（mg·prot）]与对照组[（354.35±28.12）nmol/（mg·prot）]比较急剧增高（P〈0.05）,Mel＋LPS组的MDA[（455.37±30.79）nmol/（mg·prot）]与LPS组比较则明显降低（P〈0.05）。LPS组小鼠肾组织的SOD水平[（3.75±0.23）U/（mg·prot）]与对照组[（2.93±0.29）U/（mg·prot）]比较急剧降低（P〈0.05）,Mel＋LPS组的SOD水平[（3.20±0.27）U/（mg·prot）]与LPS组比较明显增高（P〈0.05）。LPS组小鼠肾组织的HIF-1α、VEGF m RNA和蛋白水平与对照组相比急剧增高（P〈0.05）,Mel＋LPS组与LPS组比较明显降低（P〈0.05）。结论 Mel通过抑制MDA的产生和上调SOD的活性,调控HIF-1α和VEGF的表达,起到了保护LPS诱导的急性肾损伤（AKI）肾脏功能的作用。Objective To investigate the expression and influence of melatonin on hypoxia-inducible factor （HIF-1α and vascular endothelial growth factor （VEGF） in acute kidney injury induced by lipopolysaccharide （LPS）.Methods 30 Sprague-Dawly（3-5 weeks） rats were selected and randomly divided into the control group （n=10）,the LPS group （n= 10,500 μg/kg LPS was injected intravenously） and the Mel＋LPS group （n=10,melatonin was administrated orally,15 min later, LPS was given）,followed by 48 hours,the rats were killed.The thiobarbituric acid （TBA） test was given to detect thelevel of MDA and the activity of superoxide dismutase （SOD）.The mRNAs and proteins of HIF-1α and VEGF were determined by RT-qPCR and immunohistochem- istry.Results There was renal tubular epithelial cells swelling,renal interstitial edema and inflammation in the LPS group,those symptoms was attenuant in Mel ＋LSP group.The level of Scr and BUN in the LPS group[（35.56±1.83）mmol/L and （46.23±2.87）l.Lmol/L] was higher than that in the control group [（12.69±0.97）mmol/L and （16.73±1.26）μmol/L] and the Mel＋LPS group [（23.17±1.33）mmol/L and （35.67±2.25）μmol/L] （P〈0.05）.The level of MDA in the LPS group [（697.45±43.13）nmol/（mg·prot）] was higher than that in the control group [（354.35±28.12）nmol/（mg·prot）] and the ＇level of MDA in the Mel＋LPS group [（455.37±30.79）nmol/（mg .prot）] was lower than that in the LPS group （P〈0.05）.The level of SOD in the LPS group [（3.75±0.23）U/（mg·prot）] was lower than that in the control group [（2.93±0.29）U/（mg.prot）] and Mel±LPS group[（3.20±0.27）U/（mg·prot）] （P〈0.05）.The level of HIF-lot and VEGF mRNA and protein in the LPS group was higher than that in the control group,and less than that in the Mel＋LPS group.Con- clusion By inhibiting the production of MDA and up regulating the activity of SOD,Mel can regulate the expression of VEGF and HIF-1α,and plays a role in protecting LP

关 键 词：褪黑素 肾损伤低氧诱导因子1α 血管内皮生长因子 

分 类 号：R-332[医药卫生]